Tissue and circulating proprotein convertase subtilisin/Kexin type 9 (PCSK9) as promising prognostic biomarkers for curative-intent colorectal liver metastases resection: A case-control study

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of cholesterol metabolism homeostasis. However, its significance in colorectal cancer liver metastasis (CRLM) remains undetermined. Here, we evaluated PCSK9 expression and its prognostic value in patients undergoing curative-intent resection for CRLM. METHODS: We retrospectively analyzed data from 148 patients with CRLM who underwent curative-intent liver resection at Sun Yat-sen University Cancer Center between March 2009 and December 2016. We measured PCSK9 expressions in paraffin-embedded surgical specimens of CRLM using immunohistochemistry (IHC) and in plasma using enzyme-linked immunosorbent assay (ELISA). Additionally, we examined their immune profiles and correlated them with PCSK9 expression. RESULTS: PCSK9 expression was detected in 68.9 % (102/148) of the analyzed CRLM specimens. Patients with high PCSK9 expression (defined as IHC score > median) had significantly worse median OS (not reached vs. 46.2 months; hazard ratio [HR] 1.79, 95 % confidence interval [CI] 1.11-2.89; P = 0.016) and RFS (31.0 vs. 12.0 months; HR 1.85, 95 % CI 1.19-2.87; P = 0.006) compared to those with low expression. Moreover, patients with a plasma PCSK9 concentration above 75.4 ng/ml also exhibited worse OS (47.8 vs. 141.9 months, P = 0.016) and RFS (17.0 vs. 47.0 months, P = 0.047). High PCSK9 expression was associated with an increased immune proportion score (IPS) for programmed cell death-ligand 1 (PD-L1) within the metastatic site. CONCLUSIONS: Our study indicates that both tissue and plasma PCSK9 expressions hold promise as prognostic biomarkers for curative-intent resection of CRLM.